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Traffic (Copenhagen, Denmark) Jan 2015Membranes of mammalian subcellular organelles contain defined amounts of specific phospholipids that are required for normal functioning of proteins in the membrane.... (Review)
Review
Membranes of mammalian subcellular organelles contain defined amounts of specific phospholipids that are required for normal functioning of proteins in the membrane. Despite the wide distribution of most phospholipid classes throughout organelle membranes, the site of synthesis of each phospholipid class is usually restricted to one organelle, commonly the endoplasmic reticulum (ER). Thus, phospholipids must be transported from their sites of synthesis to the membranes of other organelles. In this article, pathways and subcellular sites of phospholipid synthesis in mammalian cells are summarized. A single, unifying mechanism does not explain the inter-organelle transport of all phospholipids. Thus, mechanisms of phospholipid transport between organelles of mammalian cells via spontaneous membrane diffusion, via cytosolic phospholipid transfer proteins, via vesicles and via membrane contact sites are discussed. As an example of the latter mechanism, phosphatidylserine (PS) is synthesized on a region of the ER (mitochondria-associated membranes, MAM) and decarboxylated to phosphatidylethanolamine in mitochondria. Some evidence is presented suggesting that PS import into mitochondria occurs via membrane contact sites between MAM and mitochondria. Recent studies suggest that protein complexes can form tethers that link two types of organelles thereby promoting lipid transfer. However, many questions remain about mechanisms of inter-organelle phospholipid transport in mammalian cells.
Topics: Animals; Biological Transport; Endoplasmic Reticulum; Humans; Mitochondria; Mitochondrial Membranes; Phosphatidylethanolamines; Phospholipids
PubMed: 25243850
DOI: 10.1111/tra.12230 -
IUBMB Life Jun 2010The glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic... (Review)
Review
The glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases.
Topics: Amino Acid Sequence; Animals; Humans; Molecular Sequence Data; Phosphatidylcholines; Phosphatidylethanolamines; Sequence Alignment; Signal Transduction
PubMed: 20503434
DOI: 10.1002/iub.337 -
Comprehensive Identification of Amadori Compound-Modified Phosphatidylethanolamines in Human Plasma.Chemical Research in Toxicology Jul 2019Amadori compound modified lipids are the result of nonenzymatic glycation and play an important role in several physiological and pathological processes. However,...
Amadori compound modified lipids are the result of nonenzymatic glycation and play an important role in several physiological and pathological processes. However, glycation of phosphatidylethanolamine (PE), the most abundant amine-containing lipid in blood plasma, is underexplored and so far only a few glycated PEs have been reported. Herein, we report comprehensive profiling of Amadori-PE and -LysoPE species in human plasma. Using synthetic standards, we first optimized the enrichment procedure for extracting Amadori-PE/LysoPE from plasma. On the basis of the characteristic neutral losses of 303 Da in positive and 162 Da in negative ionization mode, we then applied neural loss scanning-liquid chromatography tandem mass spectrometry (LC-NLS-MS) to identify potentially glycated PE and LysoPE, which was followed by targeted product ion scanning (LC-PIS-MS) to confidently confirm the fatty acyl substitutions of the modified lipids. A total of 20 Amadori-LysoPE and 62 Amadori-PE species, including diacyl, plasmanyl, and plasmenyl, were identified. Among them, the concentrations of 12 Amarodi-LysoPE and 54 Amadori-PE were also quantified in native human plasma, using stable isotope labeled Amadori lipids as internal standards.
Topics: Chromatography, Liquid; Glycosylation; Humans; Molecular Structure; Phosphatidylethanolamines; Tandem Mass Spectrometry
PubMed: 31188577
DOI: 10.1021/acs.chemrestox.9b00158 -
Postepy Higieny I Medycyny... Aug 2016Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are... (Review)
Review
Endocannabinoids belong to a group of ester, ether and amide derivatives of fatty acids, which are endogenous ligands of receptors CB1, CB2, TRPV1 and GPR55 that are included in the endocannabinoid system of the animal organism. The best known endocannabinoids are: N-arachidonylethanolamide called anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They occur in all organisms, and their highest level is observed in the brain. In this review the mechanisms of synthesis and degradation of both AEA and 2-AG are shown. Endocannabinoids are synthesized from phospholipids (mainly phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol) located in the cell membrane. As a result of arachidonic acid transfer from phosphatidylcholine to phosphatidylethanolamine, N-arachidonoyl phosphatidylethanolamine is formed, which is hydrolyzed to AEA by phospholipase D, C and A2. However, 2-AG is formed during the hydrolysis of phosphatidylinositol catalyzed mainly by DAGL. The primary role of endocannabinoids is the activation of cannabinoid receptors. Both AEA and 2-AG are primarily agonists of the CB1 receptor and to a lower degree CB2 and TRPV1r eceptors, but 2-AG has stronger affinity for these receptors. Through activation of receptors, endocannabinoids affect cellular metabolism and participate in the metabolic processes by receptor-independent pathways. Endocannabinoids which are not bound to the receptors are degraded. The main enzymes responsible for the hydrolysis of AEA and 2-AG are FAAH and MAGL, respectively. Apart from hydrolytic degradation, endocannabinoids may also be oxidized by cyclooxygenase-2, lipoxygenases, and cytochrome P450. It has been shown that the metabolites of both endocannabinoids also have biological significance.
Topics: Animals; Brain; Cannabinoid Receptor Modulators; Cell Membrane; Endocannabinoids; Humans; Phosphatidylethanolamines; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Cannabinoid
PubMed: 27516570
DOI: 10.5604/17322693.1213898 -
Chemistry and Physics of Lipids Jul 2021Liposomal systems are well known for playing an important role as drug carriers, presenting several therapeutic applications in different sectors, such as in drug... (Review)
Review
Liposomal systems are well known for playing an important role as drug carriers, presenting several therapeutic applications in different sectors, such as in drug delivery, diagnosis, and in many other academic areas. A novel class of this nanoparticle is the actively target liposome, which is constructed with the surface modified with appropriated molecules (or ligands) to actively bind a target molecule of certain cells, system, or tissue. There are many ways to functionalize these nanostructures, from non-covalent adsorption to covalent bond formation. In this review, we focus on the strategies of modifying liposomes by glycerophospholipid covalent chemical reaction. The approach used in this text summarizes the main reactions and strategies used in phospholipid modification that can be carried out by chemists and researchers from other areas. The knowledge of these methodologies is of great importance for planning new studies using this material and also for manipulating its properties.
Topics: Liposomes; Nanoparticles; Phosphatidylethanolamines; Phospholipids; Polyethylene Glycols; Surface Properties
PubMed: 33891960
DOI: 10.1016/j.chemphyslip.2021.105084 -
The Journal of Cell Biology Mar 2022Glycosylphosphatidylinositol (GPI) is a glycolipid membrane anchor found on surface proteins in all eukaryotes. It is synthesized in the ER membrane. Each GPI anchor...
Glycosylphosphatidylinositol (GPI) is a glycolipid membrane anchor found on surface proteins in all eukaryotes. It is synthesized in the ER membrane. Each GPI anchor requires three molecules of ethanolamine phosphate (P-Etn), which are derived from phosphatidylethanolamine (PE). We found that efficient GPI anchor synthesis in Saccharomyces cerevisiae requires Csf1; cells lacking Csf1 accumulate GPI precursors lacking P-Etn. Structure predictions suggest Csf1 is a tube-forming lipid transport protein like Vps13. Csf1 is found at contact sites between the ER and other organelles. It interacts with the ER protein Mcd4, an enzyme that adds P-Etn to nascent GPI anchors, suggesting Csf1 channels PE to Mcd4 in the ER at contact sites to support GPI anchor biosynthesis. CSF1 has orthologues in Caenorhabditis elegans (lpd-3) and humans (KIAA1109/TWEEK); mutations in KIAA1109 cause the autosomal recessive neurodevelopmental disorder Alkuraya-Kučinskas syndrome. Knockout of lpd-3 and knockdown of KIAA1109 reduced GPI-anchored proteins on the surface of cells, suggesting Csf1 orthologues in human cells support GPI anchor biosynthesis.
Topics: Autophagy; Endoplasmic Reticulum; Glycosylphosphatidylinositols; Mitochondria; Phosphatidylethanolamines; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 35015055
DOI: 10.1083/jcb.202111095 -
The Journal of Pharmacy and Pharmacology Nov 1963
Review
Topics: Biochemical Phenomena; Biochemistry; Chemistry Techniques, Analytical; Chromatography; Electrophoresis; Lysophospholipids; Phosphatidylethanolamines; Research
PubMed: 14079614
DOI: 10.1111/j.2042-7158.1963.tb12866.x -
Chemistry and Physics of Lipids 2013Glycation of phosphatidylethanolamine (PE) is a reaction that is known to occur under the chronic hyperglycemic conditions found in diabetes. Glycated...
Glycation of phosphatidylethanolamine (PE) is a reaction that is known to occur under the chronic hyperglycemic conditions found in diabetes. Glycated phosphatidylethanolamines were found in plasma and atherosclerotic plaques of diabetic patients, and its presence was correlated with increased oxidative stress. Moreover, upregulation of cytokines and other inflammatory mediators can be observed not only in diabetes, but also under oxidized phosphatidylcholine stimulation. In this study, we evaluate the effect of dipalmitoyl-phosphatidylethanolamine (DPPE) and linoleoyl-palmitoyl-phosphatidylethanolamine (PLPE) structural oxidation, glycation and glycoxidation, on monocyte and myeloid dendritic cell stimulation. Expression of cytokines, IL-1β, IL-6, IL-8, MIP-1β and TNF-α, were determined using flow cytometry after cell stimulations with native PEs, oxidized, glycated and glycoxidized PEs. Native PE, PLPE and DPPE, and all modified PEs were able to increase the stimulation levels of monocytes and mDCs. Generally, in monocytes and mDCs stimulation, GluOxPLPE and GluDPPE were the PLPE/DPPE modifications that induced the most pronounced rise in cytokine production. However, GluOxDPPE was the DPPE modification that produced the lowest stimulation levels of mDCs and monocytes. Our results indicate that glycated PE and glycoxidized PE may have an important contribution to the low-grade systemic inflammation associated with diabetes and to the development of diabetic complications.
Topics: Cytokines; Dendritic Cells; Female; Glycosylation; Humans; Male; Monocytes; Oxidation-Reduction; Phosphatidylethanolamines
PubMed: 23942208
DOI: 10.1016/j.chemphyslip.2013.07.008 -
Methods in Molecular Biology (Clifton,... 2023N-Acyl-phosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD) is a prominent enzyme involved in the biosynthesis of fatty acid amides, a family of...
N-Acyl-phosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD) is a prominent enzyme involved in the biosynthesis of fatty acid amides, a family of bioactive lipids including anandamide as the prototypical member. Here, we describe a NAPE-PLD assay based on radioactive substrates and product separation by thin layer chromatography (TLC).
Topics: Biological Assay; Chromatography, Thin Layer; Phosphatidylethanolamines; Phospholipase D
PubMed: 36152190
DOI: 10.1007/978-1-0716-2728-0_18 -
Environmental Microbiology Sep 2015All bacteria are surrounded by at least one bilayer membrane mainly composed of phospholipids (PLs). Biosynthesis of the most abundant PLs phosphatidylethanolamine (PE),... (Review)
Review
All bacteria are surrounded by at least one bilayer membrane mainly composed of phospholipids (PLs). Biosynthesis of the most abundant PLs phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and cardiolipin (CL) is well understood in model bacteria such as Escherichia coli. It recently emerged, however, that the diversity of bacterial membrane lipids is huge and that not yet explored biosynthesis pathways exist, even for the common PLs. A good example is the plant pathogen Xanthomonas campestris pv. campestris. It contains PE, PG and CL as major lipids and small amounts of the N-methylated PE derivatives monomethyl PE and phosphatidylcholine (PC = trimethylated PE). Xanthomonas campestris uses a repertoire of canonical and non-canonical enzymes for the synthesis of its membrane lipids. In this minireview, we briefly recapitulate standard pathways and integrate three recently discovered pathways into the overall picture of bacterial membrane biosynthesis.
Topics: Biosynthetic Pathways; Cardiolipins; Cell Membrane; Escherichia coli; Phosphatidylethanolamines; Phosphatidylglycerols; Plants; Xanthomonas campestris
PubMed: 26119594
DOI: 10.1111/1462-2920.12956